Gustav hildebrandt



- UNITED STATES GUSTAV HILDEBRANDT, or MANNHEIM, Annfnnwm LEUIBE'ANID WILHELM BIE Lnn,

Patented Oct; 28', 1930 or- LUDWIGSHAFENpN-THE-RHINE, GERMANY, AssIGNoRs TO No L A.-G., cnnlvnscnn FABRIKEN, or LUDWIGsnArEN-oN-rHE-rmmrz, one-many, A FIRM,

ETHYLIG-ISOPROPYL ALPHA BROMO ACETAMID Ann rnocnss' or PREPARING THE SAME No Drawing Application filed May 21, 1928, Serial Ho. 279,612, and in Germany July 27, 1926.

Our inventionrela tes to a new organic bromine preparation or compound and a method of manufacturing the same, and more partic- ,ularly to ethylic-isopropyl-alpha bromo acetamid for use as a sedative and hypnotic.

In the Germanpatent specification158,220

there is described the manufacture ofan organic compound of the formula:

R 0 Br. ooNm R.

- which possesses an eminent hypnotic effect.

' VJe have found, after much study and research, that the useful properties of the drug above referred to, that is to say, the hypnotic potency thereof, can be, highly increased and improved by substituting the isopropyl group for the propylic residue, and at the same time the toxic character of the drug will be reduced by such substitution.

In accordance with the present invention,j therefore, we manufacture the new compound,

either (1) By brominating the ethylic-isopropylacetic acid by means of phosphorus and bromine to produce a brominated acid bromide and substituting NH for the final halogen with the aid of ammonia, carbonate of ammonia or other suitable ammonium salts,

(2) By treating the acid with a phosphorus haloid, brominating the acid haloid produced by such treatment and proceeding further in the same manner as indicated in (1).

There are several other ways of manufacturing the new compound, such as by (a) Brominating the ethylic-isopropyL acetamid;

(1)) Treating the ethylic-isopropyl bromo- V acetic acid ester with ammonia;

(.0) Splitting off water from or dehydrating ethylic-isopropyl-bromo-acetate of ammonium; or

(d) Brominating nitril and subsequently saponifying the bromo-compound to obtain the amid.

We shall now proceed to describe the manufacture of the new compound more in detail by way of specific examples.

ethylic-isopropyl acetosure, until saturation is attained, the solution consisting of 200 parts by weight of thebromide compound and 1000 parts of a suitable, indifferent solvent such as ether, benzol, ligroin or the like. The ammonium bromide formed in the solution as a by-product is dissolved and-separated from the bulk by means of water and any free acid thatmay have formed in the solution is neutralized and re.-

moved .by washing the latter out with a solution of bicarbonate of sodium, whereuponthe solvent is driven off by evaporation. The re; sulting substance is thoroughly pure ethylic-J isoprop-yl-a bromo-acetic acid amid of amelting point of 51 C. The output is approximately quantitative.

Example 2.-.-1OO parts by weight of ethylic isopropyl u bronco-acetic acid chloride are mixed with to parts by weight of dry carbonate of ammonia or other suitable ammonium'salts. When the reaction is over the mixture under treatment isto bewashed successively by means of water and bicarbonate of sodium, just as in Example 1, with the re suit that the acid amid is obtained, upon re moval of the washing liquid, in the form ofan oily substance which soon congeals and be comes solid. i v y The single-steps of our manufacturing method are in themselves known, but the product resulting therefrom is novel and endowed with particularly valuable properties which are likewise novel as regards the degree or efliciency thereof, and which as compared with the known bromine compound described in the reference, characterize the new compound as an advance in the art.

In comparing the amid compound described in the reference, herein named A, with the amid compound produced in accord- In accordance with lnvestigati-ons and experiments made with guinea-pigs the lethif V erous dose of A is 0.12 gr. per kg, the narancev with the present invention, herein cotizing efiect brought about by such a dose bein very slight only, Whereas 0.1 gr. of B a per g. have a very strong narcotic effect, whilst even a dose of 0.3 gr. of B per kg. does not produce any injury to the animal.

The excessive poisonous nature of A,in comparison with B, is still more clearly evident from the following table based upon the four narcoticstages according to Sch0en see Archiv f. experiment.

Pathologie and Pharmakologie, vol. 113, page 277 of 1926 f of a, assai2 mouse 111 gr. colic stage ut '1 B A B A B l 18 l T 11 1r W 0.15 15 15 111 IV 0.21 15 15 1V n 0.32 14.5 14 5 I W 0.46 14 16 IV 1V 0.68 H 16 IV 1v I What we claim is 1. As a new article of manufacture an organic bromine compound oi? eminent narcotic character and reduced toxic nature termed ethylic isopropyl-alpha bromo-acetamid.

2. The method of producing ethylic isopropyl-alpha bromo-acetamid which comprises treating an ethylic isopropylalpha bromo-acetic haloid with ammonia so as to convert the said haloid into the acid amid.

3. The method ofproducing ethylic isopropyl-bromo acetamid which comprises dissolving an ethylic isopropyl-a bromo-acetic haloid in an organic solvent, saturating the thus obtained solution with dry ammonia gas, I washing the same subsequently with water and an alkaline solution, separating the aqueous solution from the liquid residue, and driving off the organic solvent from the lat ter by evaporation, i

In testimony whereof We affix our signatures.

DR. GUSTAV HILDEBR-ANDT. DR. ERWIN LEUBE. DR. WILHELM BIEHLER. 

